Spider Silk and Its Application in Technology and Medicine

Soft and Robust as Well

  • Fig. 1: (a) A spider silk fiber (b) exhibits a skin-core structure containing numerous fibrils (c,d) composed of a phase-separated protein matrix with nanometer-sized crystallites of alanine in ß-sheet secondary structure and glycine-rich segments embedding those nanocrystals. (e) The crystallites as well as the glycine-rich segments are highly ordered. (f) Because the crystals are interconnected through pre-stressed chains, macroscopically applied load is transferred to the molecular level, where it directly affects the nanocrystals evident in the load-dependent spectral shift of a molecular vibration.Fig. 1: (a) A spider silk fiber (b) exhibits a skin-core structure containing numerous fibrils (c,d) composed of a phase-separated protein matrix with nanometer-sized crystallites of alanine in ß-sheet secondary structure and glycine-rich segments embedding those nanocrystals. (e) The crystallites as well as the glycine-rich segments are highly ordered. (f) Because the crystals are interconnected through pre-stressed chains, macroscopically applied load is transferred to the molecular level, where it directly affects the nanocrystals evident in the load-dependent spectral shift of a molecular vibration.
  • Fig. 1: (a) A spider silk fiber (b) exhibits a skin-core structure containing numerous fibrils (c,d) composed of a phase-separated protein matrix with nanometer-sized crystallites of alanine in ß-sheet secondary structure and glycine-rich segments embedding those nanocrystals. (e) The crystallites as well as the glycine-rich segments are highly ordered. (f) Because the crystals are interconnected through pre-stressed chains, macroscopically applied load is transferred to the molecular level, where it directly affects the nanocrystals evident in the load-dependent spectral shift of a molecular vibration.
  • Fig. 2: Natural spider silk fibers can be employed in traumatically injured peripheral nerves in order to induce and direct nerve healing. Additionally, they can act in (non-)woven meshes as wound coverage or platform for artificial skin generation; in woven meshes as replacement for tissues; in braided forms as tendon repair or suture. On the basis of recombinant silk proteins one is able to produce fibers, but also non-woven meshes for air filter devices, foams as matrices for cell culturing, micro particles as drug delivery systems or coatings or non-woven meshes to reduce immune response to implants.
A. M. Anton1 and F. Kremer1
 
Spider silk (exactly, the silk of the major ampullate glands or dragline silk) has been attracted attention for decades. It is soft and elastic but, while only a few micrometers thick, surprisingly resistant against tensile stress. Thus, silk shows the highest toughness –dissipated energy per unit volume– than any other material [1]. Furthermore, silk or its proteins provide versatile possibilities for tissue engineering and implant coating, because of their immunological tolerance. Moreover, it is the first natural material that shows a phononic band gap and negative dispersion relation, which was until recently solely known for artificial metamaterials [2]. Since spiders behave territorially and cannibalistically, the production of spider silk in a similar manner to silkworm silk is limited. In order to manufacture comparable materials, silk’s architecture on the mesoscopic and molecular scale as well as the impact of those on the material’s properties has to be understood. In this article we review the unique morphology and functional structure of spider silk and present versatile applications. 
 
Spider Silk’s Molecular Architecture
 
The mechanical properties of spider silk arise from a refined architecture on different length scales. A single thread has a skin-core structure with numerous fibrils (fig. 1a-c), which are composed of a phase-separated matrix of two spider silk proteins (major ampullate spidroin I and II, MaSpI and MaSpII, fig. 1d). Both exhibit a block-like primary structure with alternating polyalanine (An) and glycine-rich segments ((GGX)n and (GPGXX)n). During spinning the proteins experience shear force which orients them and induce a structural conversion. The An parts adopt a ß-sheet secondary structure forming nanometer-sized crystallites (5×5×7 nm3) and the glycine-rich segments embed the crystals in a matrix, while the orientation and order of all molecular segments is well preserved on macroscopic scale (fig.

e) [1]. Furthermore, IR spectroscopy in combination with external mechanical fields performed by Prof. Dr. Friedrich Kremer and coworkersa proved that the nanocrystals are interconnected through pre-stressed protein chains [3, 4]. Thereby, the tendency to contract is counterbalance by the crystal-surrounding protein matrix. As a consequence of this refined construction macroscopically applied load is transferred through the soft matrix down to the molecular scale where it acts on the much stronger crystallites, which finally dissipate the impinging energy. This exceptional mechanism manifests itself in the load dependence of a molecular vibration that is exclusively located within those crystallites. In case tensile stress is applied to the silk fiber, the molecular stress acting on the nanocrystals is increased and a red shift of the crystal-specific IR absorption band occurs (fig. 1f). In the opposite case, when hydrostatic pressure is applied, the molecular stress is reduced and the crystal band shows a blue shift.

 
Manufacturing of Artificial Silk
 
In order to elevate spider silk production to industrial scale, the manufacturing of recombinant proteins has to be developed. In one approach Prof. Dr. David L. Kaplan and coworkersb inserted DNA encoding spider silk proteins into prokaryotes as Escherichia coli bacteria [5] or by other researchers into eukaryotes as Pichia pastoris yeast [6], which then expressed these proteins. The transfection and expression works also with mammalian cells like bovine mammary epithelial alveolar and baby hamster kidney cells as Dr. Anthoula Lazaris and coworkersc has demonstrated [7]. Alternatively, transgenetic goats, which produced milk including spider silk proteins, and transgenetic plants has been tested by Prof. Dr. Randolph V. Lewis and coworkersd [8], but both projects were put on hold in the meantime. However, performing sericulture with transgenetic silkworms that produce chimeric silkworm/spider silk fibers as published by Prof. Dr. Malcolm J. Frasere, Jr., Prof. Dr. Randolph V. Lewisf, Prof. Dr. Donald L. Jarvisd, and coworkers may be another promising solution. The first recombinant spider silk with comparable toughness as natural major ampullate silk was published in 2015 by Prof. Dr. Thomas Scheibel and coworkersg [9].
 
Applications in Technique
 
Silk has a long history as protective material. Except for body armors, silkworm silk has also been employed in parachutes. Although spider silk provides superior mechanical resistance compared to silkworm silk, problems as spiders’ cannibalism did prevent industrial farming comparable to sericulture in the past. By means of the new production methods, spider silk will become more prominent; actually the U.S. Army is testing spider silk for body armors (The Washington Times, July 12, 2016).
Besides mechanical demanding applications, spider silk may play an important role in future photonics and electronics. Nowadays, silkworm silk can be prepared as optical device like contact lenses, optical waveguides, and 3D diffraction patterns [10]. When casting silk solution over a template of close-packed colloidal particles a 3D photonic crystal of silk invers opals is obtained. Its color may be modified by the casting template or filling. In addition it is suited as optical humidity sensor [11, 17].
 
Application in Medicine
 
Spider silk holds great potential in the medical sector. Native silk is excellently biocompatible while suppressing inflammations and promoting cell adhesion. It is suited as suture (fig. 2; fibers, meshes) or replacement for tissues as Prof. Dr. Kerstin Reimers-Fadhlaoui and coworkersh figured out [12-14]. As published by Prof. Dr. Thomas Scheibel and coworkersg, a coating of recombinant spider silk proteins onto a silicone implant prevents post-operative inflammatory and fibrotic complications [15].
Nowadays, silkworm silk-based materials provide an ideal matrix for stabilizing enzymes or antigens, which may work as disease detecting biosensors (films) or drug delivery systems (particles) [10]. Prof. Dr. David L. Kaplanb, Prof. Dr. Fiorenzo G. Omenettob, and coworkers demonstrated the formation of conformal electronics as biointegrated devices for diagnosing or brain/machine interfaces [11, 16, 18]. Moreover, silkworm silk implants are tested by Prof. Dr. Fritz Vollrathi and coworkers as bone or cartilage growing templates (foams).
 
Summary
 
Spider silk provides versatile opportunities for high tensile robustness applications but also for excellent biocompatibility requirements. Repairing traumatically interrupted nerve cells appears possible as well as integrate electronic into living organisms. As soon as spider silk will be available in industrial quantities, it will capture a share in the market, which is at the moment dominated by silkworm silk.
 
Affiliation
 
1 University of Leipzig, Institute for Experimental Physics, Leipzig, Germany
 
Contact
Prof. Dr. Friedrich Kremer
University of Leipzig
Institute for Experimental Physics
Leipzig, Germany
kremer@physik.uni-leipzig.de
 
More articles on spider silk: http://www.laboratory-journal.com/category/tags/spider-silk
 
More information: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658765/
 

Affiliations of Cited Authors
a University of Leipzig, Germany
b Tufts University, USA
c McGill University, Canada
d University of Wyoming, USA
e University of Notre Dame, USA
f Utah State University, USA
g University of Bayreuth, Germany
h Hannover Medical School, Germany
i Oxford University, UK

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